Cytomegalovirus-specific T-cell responses and viral replication in kidney transplant recipients
<p>Abstract</p> <p>Background</p> <p>Cytomegalovirus (CMV) seronegative recipients (R-) of kidney transplants (KT) from seropositive donors (D+) are at higher risk for CMV replication and ganciclovir(GCV)-resistance than CMV R(+). We hypothesized that low CMV-specific T...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2008-06-01
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| Series: | Journal of Translational Medicine |
| Online Access: | http://www.translational-medicine.com/content/6/1/29 |
| _version_ | 1828738904536121344 |
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| author | Sester Urban Steiger Juerg Schaub Stefan Dumoulin Alexis Jäger Clemens Binggeli Simone Binet Isabelle Egli Adrian Sester Martina Hirsch Hans H |
| author_facet | Sester Urban Steiger Juerg Schaub Stefan Dumoulin Alexis Jäger Clemens Binggeli Simone Binet Isabelle Egli Adrian Sester Martina Hirsch Hans H |
| author_sort | Sester Urban |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Cytomegalovirus (CMV) seronegative recipients (R-) of kidney transplants (KT) from seropositive donors (D+) are at higher risk for CMV replication and ganciclovir(GCV)-resistance than CMV R(+). We hypothesized that low CMV-specific T-cell responses are associated with increased risk of CMV replication in R(+)-patients with D(+) or D(-) donors.</p> <p>Methods</p> <p>We prospectively evaluated 73 consecutive KT-patients [48 R(+), 25 D(+)R(-)] undergoing routine testing for CMV replication as part of a preemptive strategy. We compared CMV-specific interferon-γ (IFN-γ) responses of CD4+CD3+ lymphocytes in peripheral blood mononuclear cells (PBMC) using three different antigen preparation (CMV-lysate, pp72- and pp65-overlapping peptide pools) using intracellular cytokine staining and flow cytometry.</p> <p>Results</p> <p>Median CD4+ and CD8+T-cell responses to CMV-lysate, pp72- and pp65-overlapping peptide pools were lower in D(+)R(-) than in R(+)patients or in non-immunosuppressed donors. Comparing subpopulations we found that CMV-lysate favored CD4+- over CD8+-responses, whereas the reverse was observed for pp72, while pp65-CD4+- and -CD8+-responses were similar. Concurrent CMV replication in R(+)-patients was associated with significantly lower T-cell responses (pp65 median CD4+ 0.00% vs. 0.03%, p = 0.001; CD8+ 0.01% vs. 0.03%; p = 0.033). Receiver operated curve analysis associated CMV-pp65 CD4+ responses of > 0.03% in R(+)-patients with absence of concurrent (p = 0.003) and future CMV replication in the following 8 weeks (p = 0.036). GCV-resistant CMV replication occurred in 3 R(+)-patients (6.3%) with pp65- CD4+ frequencies < 0.03% (p = 0.041).</p> <p>Conclusion</p> <p>The data suggest that pp65-specific CD4+ T-cells might be useful to identify R(+)-patients at increased risk of CMV replication. Provided further corroborating evidence, CMV-pp65 CD4+ responses above 0.03% in PBMCs of KT patients under stable immunosuppression are associated with lower risk of concurrent and future CMV replication during the following 8 weeks.</p> |
| first_indexed | 2024-04-13T00:12:09Z |
| format | Article |
| id | doaj.art-3484513149534b48a86ef6ba5bc2c3f6 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-13T00:12:09Z |
| publishDate | 2008-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-3484513149534b48a86ef6ba5bc2c3f62022-12-22T03:11:02ZengBMCJournal of Translational Medicine1479-58762008-06-01612910.1186/1479-5876-6-29Cytomegalovirus-specific T-cell responses and viral replication in kidney transplant recipientsSester UrbanSteiger JuergSchaub StefanDumoulin AlexisJäger ClemensBinggeli SimoneBinet IsabelleEgli AdrianSester MartinaHirsch Hans H<p>Abstract</p> <p>Background</p> <p>Cytomegalovirus (CMV) seronegative recipients (R-) of kidney transplants (KT) from seropositive donors (D+) are at higher risk for CMV replication and ganciclovir(GCV)-resistance than CMV R(+). We hypothesized that low CMV-specific T-cell responses are associated with increased risk of CMV replication in R(+)-patients with D(+) or D(-) donors.</p> <p>Methods</p> <p>We prospectively evaluated 73 consecutive KT-patients [48 R(+), 25 D(+)R(-)] undergoing routine testing for CMV replication as part of a preemptive strategy. We compared CMV-specific interferon-γ (IFN-γ) responses of CD4+CD3+ lymphocytes in peripheral blood mononuclear cells (PBMC) using three different antigen preparation (CMV-lysate, pp72- and pp65-overlapping peptide pools) using intracellular cytokine staining and flow cytometry.</p> <p>Results</p> <p>Median CD4+ and CD8+T-cell responses to CMV-lysate, pp72- and pp65-overlapping peptide pools were lower in D(+)R(-) than in R(+)patients or in non-immunosuppressed donors. Comparing subpopulations we found that CMV-lysate favored CD4+- over CD8+-responses, whereas the reverse was observed for pp72, while pp65-CD4+- and -CD8+-responses were similar. Concurrent CMV replication in R(+)-patients was associated with significantly lower T-cell responses (pp65 median CD4+ 0.00% vs. 0.03%, p = 0.001; CD8+ 0.01% vs. 0.03%; p = 0.033). Receiver operated curve analysis associated CMV-pp65 CD4+ responses of > 0.03% in R(+)-patients with absence of concurrent (p = 0.003) and future CMV replication in the following 8 weeks (p = 0.036). GCV-resistant CMV replication occurred in 3 R(+)-patients (6.3%) with pp65- CD4+ frequencies < 0.03% (p = 0.041).</p> <p>Conclusion</p> <p>The data suggest that pp65-specific CD4+ T-cells might be useful to identify R(+)-patients at increased risk of CMV replication. Provided further corroborating evidence, CMV-pp65 CD4+ responses above 0.03% in PBMCs of KT patients under stable immunosuppression are associated with lower risk of concurrent and future CMV replication during the following 8 weeks.</p>http://www.translational-medicine.com/content/6/1/29 |
| spellingShingle | Sester Urban Steiger Juerg Schaub Stefan Dumoulin Alexis Jäger Clemens Binggeli Simone Binet Isabelle Egli Adrian Sester Martina Hirsch Hans H Cytomegalovirus-specific T-cell responses and viral replication in kidney transplant recipients Journal of Translational Medicine |
| title | Cytomegalovirus-specific T-cell responses and viral replication in kidney transplant recipients |
| title_full | Cytomegalovirus-specific T-cell responses and viral replication in kidney transplant recipients |
| title_fullStr | Cytomegalovirus-specific T-cell responses and viral replication in kidney transplant recipients |
| title_full_unstemmed | Cytomegalovirus-specific T-cell responses and viral replication in kidney transplant recipients |
| title_short | Cytomegalovirus-specific T-cell responses and viral replication in kidney transplant recipients |
| title_sort | cytomegalovirus specific t cell responses and viral replication in kidney transplant recipients |
| url | http://www.translational-medicine.com/content/6/1/29 |
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